10-102918527-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_017649.5(CNNM2):c.47G>A(p.Gly16Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,604,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017649.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNNM2 | NM_017649.5 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 8 | ENST00000369878.9 | NP_060119.3 | |
CNNM2 | NM_199076.3 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 7 | NP_951058.1 | ||
CNNM2 | NM_199077.3 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 2 | NP_951059.1 | ||
LOC107984265 | NR_160733.1 | n.-192C>T | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNNM2 | ENST00000369878.9 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 8 | 1 | NM_017649.5 | ENSP00000358894.3 | ||
CNNM2 | ENST00000369875.3 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 2 | 1 | ENSP00000358891.3 | |||
CNNM2 | ENST00000433628.2 | c.47G>A | p.Gly16Glu | missense_variant | Exon 1 of 7 | 2 | ENSP00000392875.2 | |||
ENSG00000286575 | ENST00000652934.1 | n.-192C>T | upstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000574 AC: 13AN: 226442Hom.: 0 AF XY: 0.0000478 AC XY: 6AN XY: 125436
GnomAD4 exome AF: 0.000163 AC: 237AN: 1452094Hom.: 0 Cov.: 31 AF XY: 0.000151 AC XY: 109AN XY: 722312
GnomAD4 genome AF: 0.000144 AC: 22AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:4
CNNM2: PM2:Supporting, PP2 -
This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 16 of the CNNM2 protein (p.Gly16Glu). This variant is present in population databases (rs370580602, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CNNM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1430577). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Renal hypomagnesemia 6;C4225333:Hypomagnesemia, seizures, and intellectual disability 1 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at